ABSTRACT
Várias doenças estão relacionadas ao tabagismo, mas não se sabe ao certo o momento em que os malefícios superamos mecanismos de defesa do organismo. O objetivo deste trabalho foi verificar as alterações bioquímicas, hematológicas e imunológicas, em adultos jovens fumantes, comparando com adultos jovens, não fumantes. Vinte e quatro não-fumantes e 14 fumantes (fumam há 8 mais ou menos 1 ano, e uma quantidade média de cigarros/dia = 10 mais ou menos 4,9), alunos da UNISO dos cursos da saúde (Farmácia, Nutrição e Terapia Ocupacional), com idade média de 23 mais ou menos 3,6 anos, participaram do estudo. As amostras de sangue foram coletadas de acordo com as exigências para as seguintes análises: colesterol total, HDL-colesterol, LDL-colesterol, VLDL-colesterol, triacilgliceróis, glicose, uréia, ácido úrico e creatinina sérica. Os grupos demonstraram ser normolipidêmicos, euglicêmicos, com valores séricos de uréia, creatinina, ácido úrico, proteína C reativa (PCR), imunoglobulinas G (IgG) e M (IgM), complemento C3 e contagem global de glóbulos brancos e vermelhos, dentro dos valores de referência. A maior concentração sérica da uréia foi observada no grupo de fumantes e nenhuma outra diferença significativa foi observada entre os grupos, indicando talvez que a duração do tabagismo não foi ainda suficiente para alterar algum parâmetro laboratorial
Subject(s)
Humans , Male , Female , Adult , Case-Control Studies , Statistics, Nonparametric , Tobacco Use Disorder/adverse effects , Tobacco Use Disorder/immunology , Tobacco Use Disorder/bloodABSTRACT
The relationships between structures and inhibitory activities of glycosidase inhibitors of gem-diamine 1-N-iminosugars in media of enzyme assays have been investigated. It has been proved that gem-diamine 1-N-iminosugar smoothly undergoes a structural change to a hydrated ketone or its derivative via a hemiaminal in the media (pH 5.0-6.3), and that the products generated in the media as well as the parent gem-diamine 1-N-iminosugars potently inhibit glycosidases.
Subject(s)
Carbohydrate Metabolism , Enzyme Inhibitors/metabolism , Glycoside Hydrolases/metabolism , Ketones/metabolism , alpha-L-Fucosidase/metabolism , Animals , Carbohydrates/chemistry , Carbohydrates/pharmacology , Diamines/chemistry , Enzyme Inhibitors/pharmacology , Glycoside Hydrolases/antagonists & inhibitors , Hydrogen-Ion Concentration , Imines/chemistry , Ketones/chemistry , Ketones/pharmacology , Structure-Activity Relationship , Time Factors , alpha-L-Fucosidase/antagonists & inhibitorsABSTRACT
[reaction: see text] 6-Acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)-3-piperidinecarboxylic acids (8 and 9) have been synthesized starting from natural siastatin B, a bacterial neuraminidase inhibitor isolated from Streptomyces culture in a stereospecific fashion. These compounds are related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.
Subject(s)
Acetamides/chemistry , Acetamides/chemical synthesis , Antiviral Agents/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Neuraminidase/antagonists & inhibitors , Orthomyxoviridae/enzymology , Piperidines/chemical synthesis , Sialic Acids/chemistry , Acetamides/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Clostridium perfringens/enzymology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Guanidines , Oseltamivir , Piperidines/chemistry , Piperidines/pharmacology , Pyrans , ZanamivirABSTRACT
An efficient and general synthetic route to all eight stereoisomeric D-glycono-delta-lactams has been developed. The strategy involves, as a key step, a stereodivergent delta-lactam formation with configurational retention or inversion at C-4 of a starting gamma-lactone to lead to two epimers of delta-lactam from one parent gamma-lactone. Conformations of eight glycono-delta-lactams were examined by X-ray crystallographic analysis and molecular modeling. Analyses of conformation and glycosidase-inhibition provide useful information for the design of new glycosidase inhibitors.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Lactams/chemical synthesis , Animals , Aspergillus niger/enzymology , Carbohydrate Conformation , Enzyme Inhibitors/pharmacology , Kinetics , Lactams/chemistry , Lactams/pharmacology , Mannosidases/antagonists & inhibitors , Models, Chemical , Models, Molecular , Saccharomyces cerevisiae , Snails , Stereoisomerism , Structure-Activity Relationship , alpha-Mannosidase , beta-Glucosidase/antagonists & inhibitorsABSTRACT
An efficient and flexible synthetic route to four gem-diamine 1-N-iminosugars of uronic acid-type (D-glucuronic, D-mannuronic, L-iduronic, and L-guluronic acid), a new family of glycosidase inhibitor, from l-galactono-1,4-lactone have been developed in an enantiodivergent fashion through a sequence involving as the key steps (a) the formation of gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal and (b) the introduction of a carboxylic acid group by the Wittig reaction of a ketone, hydroboration and oxidation, and the Sharpless oxidation. D-Glucuronic and D-mannuronic acid-type 1-N-iminosugars, (3S,4R,5R, 6R)- and (3S,4R,5R,6S)-4, 5-dihydroxy-6-trifluoroacetamido-3-piperidinecarboxylic acid, were proven to be potent inhibitors for beta-D-glucuronidase (IC(50) 6.5 x 10(-)(8)M) and to affect human heparanase (endo-beta-glucuronidase).
Subject(s)
Carbohydrates/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Uronic Acids/chemistry , Animals , Carbohydrate Conformation , Carbohydrates/chemistry , Carbohydrates/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Humans , Imines/chemistry , Magnetic Resonance Spectroscopy , Models, MolecularABSTRACT
An efficient route from D-ribono-gamma-lactone to gem-diamine 1-N-iminosugars of L-fucose-type, a new family of glycosidase inhibitor, has been developed in a formation of a gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal as a key step. The analogues were proved to be the extremely potent inhibitors against alpha-L-fucosidase (IC50 approximately 3 ng mL(-1), Ki approximately 5 x 10(-9) M). The present study has shown that a cyclic methanediamine generated in media affects glycosidases as a real active-form of the gem-diamine 1-N-iminosugars of L-fucose-type.
Subject(s)
Carbohydrates/pharmacology , Enzyme Inhibitors/pharmacology , alpha-L-Fucosidase/antagonists & inhibitors , Carbohydrate Sequence , Carbohydrates/chemical synthesis , Carbohydrates/chemistry , Diamines/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Imines/chemistry , Molecular Sequence Data , Molecular Structure , Spectrum AnalysisABSTRACT
gem-Diamine 1-N iminosugars of D-glucose-type, a new type of glycosidase inhibitors, have been synthesized from siastatin B, isolated from Streptomyces culture. 2-Trifluoroacetamido-1-N-iminosugar, (2S,3R,4R,5R)-2-trifluoroacetamido-5-hydroxymethylpiperidine -3,4-diol was proved to be a potent inhibitor for alpha-D- and beta-D-glucosidases (IC50 1.9x10(-7) and 4.2x10(-7) M, respectively). 2-Acetamido-1-N-iminosugar, (2S,3R,4R,5R)-2-acetamido-5-hydroxymethylpiperidine-3,4-diol also affected these enzymes (IC50 2.9x10(-6) and 5.4x10(-6) M, respectively).
Subject(s)
Enzyme Inhibitors/chemical synthesis , Glucosidases/antagonists & inhibitors , Piperidines/chemical synthesis , Aspergillus niger/enzymology , Enzyme Inhibitors/pharmacology , Glucosidases/metabolism , Piperidines/isolation & purification , Piperidines/pharmacology , Streptomyces/chemistryABSTRACT
The reaction of cyanogen bromide (1) with primary amines (2a-p), including arylmethylamines (2l-p), gave the corresponding cyanamides (3a-p). Trimerization of 3a-p gave 1,3,5-trisubstituted 2,4,6-triiminohexahydro-1,3,5-triazines (isomelamines) (4a-p), which were treated with hydrochloric acid to give the corresponding 1,3,5-trisubstituted 2,4,6-trioxohexahydro-1,3,5-triazines (isocyanurates) (5a-c, f) and 1,3,5-trisubstituted 2-imino-4,6-dioxohexahydro-1,3,5-triazines (5b'-e'). Biological evaluation of 4a-p, 5a-c,f, and 5b'-e' was carried out, and some of these compounds showed bronchodilator and positive inotropic activities.